BH3 Domains of BH3-Only Proteins Differentially Regulate Bax-Mediated Mitochondrial Membrane Permeabilization Both Directly and Indirectly
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چکیده
منابع مشابه
Bax and BH3-domain-only proteins in p53-mediated apoptosis.
Activation of mitochondria-mediated apoptosis represents a major anti-tumor response of p53. One of the mechanisms for p53 to induce mitochondria-mediated cell death events is to activate genes that are directly involved in the initiation of mitochondria-induced apoptosis. Among them are Bcl-2 family members, Noxa, PUMA, and Bax. They have been shown to be direct targets in p53-mediated apoptos...
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Although the mechanisms by which Bcl-2 family proteins control the apoptotic machinery of the cell are not fully understood, it becomes clear that the role of BH3-only proteins consists in serving as sensors or sentinels of cellular damage, transducing the apoptotic stimuli to the mitochondria. For this reason, mammalian cells have developed several strategies for their strict regulation throug...
متن کاملBH3 domains other than Bim and Bid can directly activate Bax/Bak.
Bcl-2 family proteins regulate a critical step in apoptosis referred to as mitochondrial outer membrane permeabilization (MOMP). Members of a subgroup of the Bcl-2 family, known as the BH3-only proteins, activate pro-apoptotic effectors (Bax and Bak) to initiate MOMP. They do so by neutralizing pro-survival Bcl-2 proteins and/or directly activating Bax/Bak. Bim and Bid are reported to be direct...
متن کاملStructure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1.
Pro-survival proteins in the B-cell lymphoma-2 (Bcl-2) family have a defined specificity profile for their cell death-inducing BH3-only antagonists. Solution structures of myeloid cell leukaemia-1 (Mcl-1) in complex with the BH3 domains from Noxa and Puma, two proteins regulated by the tumour suppressor p53, show that they bind as amphipathic alpha-helices in the same hydrophobic groove of Mcl-...
متن کاملBCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis.
Critical issues in apoptosis include the importance of caspases versus organelle dysfunction, dominance of anti- versus proapoptotic BCL-2 members, and whether commitment occurs upstream or downstream of mitochondria. Here, we show cells deficient for the downstream effectors Apaf-1, Caspase-9, or Caspase-3 display only transient protection from "BH3 domain-only" molecules and die a caspase-ind...
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ژورنال
عنوان ژورنال: Molecular Cell
سال: 2005
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2005.02.003